Dexmedetomidine may offer alternative to midazolam or propofol in ICU sedation

Abstract

MedWire News: Dexmedetomidine is no less effective than either midazolam or propofol in maintaining correct sedation levels in patients on long-term mechanical ventilation in the intensive care unit (ICU), according to findings from the MIDEX and PRODEX studies.

Patients in the ICU can often benefit from sedation if they experience continuous discomfort from procedures or mechanical ventilation. However, currently available sedating agents, such as propofol and benzodiazepines, can have potentially fatal side effects.

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Dexmedetomidine is a sedative with α2-adrenoreceptor action and affinity in the locus ceruleus. Its use in the ICU has been found to cause less delirium than midazolam, though its effectiveness on duration of ICU stay and mechanical ventilation use was not definitively determined.

Jukka Takala (Bern University Hospital, Switzerland) and colleagues conducted two separate multicenter, double-blind, phase III studies of dexmedetomidine, one comparing it with midazolam (MIDEX) and one with propofol (PRODEX). Eligible patients (about 500 for each study) were aged 18 years or older and were on mechanical ventilation in the ICU. The primary endpoints were noninferiority of dexmedetomidine to either agent in terms of proportion of time at target sedation level, and superiority of dexmedetomidine regarding mechanical ventilation duration. Results are reported in JAMA.

The noninferiority of dexmedetomidine was confirmed in both studies, although rates of discontinuation of treatment due to lack of efficacy and incidence of bradycardia and hypotension were greater in those given dexmedetomidine.

Patients given dexmedetomidine were on mechanical ventilation for less time and were able to communicate better than patients given either midazolam or propofol.

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There were no significant differences in length of ICU stay between the groups in either study.

Takala and colleagues note that dexmedetomidine was used for light to moderate sedation in these trials, as it may not be appropriate for heavy sedation. They also acknowledge that patients were not directly asked about the quality of sedation experienced with any of the agents.

In a related editorial, Hannah Wunsch (Columbia University College of Physicians & Surgeons, New York, USA) remarks that heavy sedation in the ICU can impede certain treatment goals, such as weaning patients off ventilators, and that an agent such as dexmedetomidine is a feasible alternative. It has not been as widely used as older agents due to higher costs and lack of clinical data. Now, they say, the MIDEX and PRODEX trials "provide important evidence that dexmedetomidine is an effective sedative compared with both midazolam and propofol."

"When there is no longer a need to weigh the drug acquisition costs, even uncertain improvements in the patient experience should be justification enough for broader use of dexmedetomidine in the ICU," the team concludes.